Kyoungjae Lee, Jaeyong Lee, Lizhen Lin.

Source: The Annals of Statistics, Volume 47, Number 6, 3413--3437.

Abstract:
In this paper we study the high-dimensional sparse directed acyclic graph (DAG) models under the empirical sparse Cholesky prior. Among our results, strong model selection consistency or graph selection consistency is obtained under more general conditions than those in the existing literature. Compared to Cao, Khare and Ghosh [ Ann. Statist. (2019) 47 319–348], the required conditions are weakened in terms of the dimensionality, sparsity and lower bound of the nonzero elements in the Cholesky factor. Furthermore, our result does not require the irrepresentable condition, which is necessary for Lasso-type methods. We also derive the posterior convergence rates for precision matrices and Cholesky factors with respect to various matrix norms. The obtained posterior convergence rates are the fastest among those of the existing Bayesian approaches. In particular, we prove that our posterior convergence rates for Cholesky factors are the minimax or at least nearly minimax depending on the relative size of true sparseness for the entire dimension. The simulation study confirms that the proposed method outperforms the competing methods.

James G. Scott, James O. Berger

Source: Ann. Statist., Volume 38, Number 5, 2587--2619.

Abstract:
This paper studies the multiplicity-correction effect of standard Bayesian variable-selection priors in linear regression. Our first goal is to clarify when, and how, multiplicity correction happens automatically in Bayesian analysis, and to distinguish this correction from the Bayesian Ockham’s-razor effect. Our second goal is to contrast empirical-Bayes and fully Bayesian approaches to variable selection through examples, theoretical results and simulations. Considerable differences between the two approaches are found. In particular, we prove a theorem that characterizes a surprising aymptotic discrepancy between fully Bayes and empirical Bayes. This discrepancy arises from a different source than the failure to account for hyperparameter uncertainty in the empirical-Bayes estimate. Indeed, even at the extreme, when the empirical-Bayes estimate converges asymptotically to the true variable-inclusion probability, the potential for a serious difference remains.

Wanghuan Chu, Runze Li, Jingyuan Liu, Matthew Reimherr.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 276--298.

Abstract:
Motivated by an empirical analysis of data from a genome-wide association study on obesity, measured by the body mass index (BMI), we propose a two-step gene-detection procedure for generalized varying coefficient mixed-effects models with ultrahigh dimensional covariates. The proposed procedure selects significant single nucleotide polymorphisms (SNPs) impacting the mean BMI trend, some of which have already been biologically proven to be “fat genes.” The method also discovers SNPs that significantly influence the age-dependent variability of BMI. The proposed procedure takes into account individual variations of genetic effects and can also be directly applied to longitudinal data with continuous, binary or count responses. We employ Monte Carlo simulation studies to assess the performance of the proposed method and further carry out causal inference for the selected SNPs.

Li Zhu, Zhiguang Huo, Tianzhou Ma, Steffi Oesterreich, George C. Tseng.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2611--2636.

Abstract:
Variable selection is a pervasive problem in modern high-dimensional data analysis where the number of features often exceeds the sample size (a.k.a. small-n-large-p problem). Incorporation of group structure knowledge to improve variable selection has been widely studied. Here, we consider prior knowledge of a hierarchical overlapping group structure to improve variable selection in regression setting. In genomics applications, for instance, a biological pathway contains tens to hundreds of genes and a gene can be mapped to multiple experimentally measured features (such as its mRNA expression, copy number variation and methylation levels of possibly multiple sites). In addition to the hierarchical structure, the groups at the same level may overlap (e.g., two pathways can share common genes). Incorporating such hierarchical overlapping groups in traditional penalized regression setting remains a difficult optimization problem. Alternatively, we propose a Bayesian indicator model that can elegantly serve the purpose. We evaluate the model in simulations and two breast cancer examples, and demonstrate its superior performance over existing models. The result not only enhances prediction accuracy but also improves variable selection and model interpretation that lead to deeper biological insight of the disease.

Federico Castelletti, Guido Consonni.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2289--2311.

Abstract:
A signalling pathway is a sequence of chemical reactions initiated by a stimulus which in turn affects a receptor, and then through some intermediate steps cascades down to the final cell response. Based on the technique of flow cytometry, samples of cell-by-cell measurements are collected under each experimental condition, resulting in a collection of interventional data (assuming no latent variables are involved). Usually several external interventions are applied at different points of the pathway, the ultimate aim being the structural recovery of the underlying signalling network which we model as a causal Directed Acyclic Graph (DAG) using intervention calculus. The advantage of using interventional data, rather than purely observational one, is that identifiability of the true data generating DAG is enhanced. More technically a Markov equivalence class of DAGs, whose members are statistically indistinguishable based on observational data alone, can be further decomposed, using additional interventional data, into smaller distinct Interventional Markov equivalence classes. We present a Bayesian methodology for structural learning of Interventional Markov equivalence classes based on observational and interventional samples of multivariate Gaussian observations. Our approach is objective, meaning that it is based on default parameter priors requiring no personal elicitation; some flexibility is however allowed through a tuning parameter which regulates sparsity in the prior on model space. Based on an analytical expression for the marginal likelihood of a given Interventional Essential Graph, and a suitable MCMC scheme, our analysis produces an approximate posterior distribution on the space of Interventional Markov equivalence classes, which can be used to provide uncertainty quantification for features of substantive scientific interest, such as the posterior probability of inclusion of selected edges, or paths.

Gabriela V. Cohen Freue, David Kepplinger, Matías Salibián-Barrera, Ezequiel Smucler.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2065--2090.

Abstract:
In large-scale quantitative proteomic studies, scientists measure the abundance of thousands of proteins from the human proteome in search of novel biomarkers for a given disease. Penalized regression estimators can be used to identify potential biomarkers among a large set of molecular features measured. Yet, the performance and statistical properties of these estimators depend on the loss and penalty functions used to define them. Motivated by a real plasma proteomic biomarkers study, we propose a new class of penalized robust estimators based on the elastic net penalty, which can be tuned to keep groups of correlated variables together in the selected model and maintain robustness against possible outliers. We also propose an efficient algorithm to compute our robust penalized estimators and derive a data-driven method to select the penalty term. Our robust penalized estimators have very good robustness properties and are also consistent under certain regularity conditions. Numerical results show that our robust estimators compare favorably to other robust penalized estimators. Using our proposed methodology for the analysis of the proteomics data, we identify new potentially relevant biomarkers of cardiac allograft vasculopathy that are not found with nonrobust alternatives. The selected model is validated in a new set of 52 test samples and achieves an area under the receiver operating characteristic (AUC) of 0.85.

Lin Liu, Yuqi Qiu, Loki Natarajan, Karen Messer.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1370--1396.

Abstract:
It is common to encounter missing data among the potential predictor variables in the setting of model selection. For example, in a recent study we attempted to improve the US guidelines for risk stratification after screening colonoscopy ( Cancer Causes Control 27 (2016) 1175–1185), with the aim to help reduce both overuse and underuse of follow-on surveillance colonoscopy. The goal was to incorporate selected additional informative variables into a neoplasia risk-prediction model, going beyond the three currently established risk factors, using a large dataset pooled from seven different prospective studies in North America. Unfortunately, not all candidate variables were collected in all studies, so that one or more important potential predictors were missing on over half of the subjects. Thus, while variable selection was a main focus of the study, it was necessary to address the substantial amount of missing data. Multiple imputation can effectively address missing data, and there are also good approaches to incorporate the variable selection process into model-based confidence intervals. However, there is not consensus on appropriate methods of inference which address both issues simultaneously. Our goal here is to study the properties of model-based confidence intervals in the setting of imputation for missing data followed by variable selection. We use both simulation and theory to compare three approaches to such post-imputation-selection inference: a multiple-imputation approach based on Rubin’s Rules for variance estimation ( Comput. Statist. Data Anal. 71 (2014) 758–770); a single imputation-selection followed by bootstrap percentile confidence intervals; and a new bootstrap model-averaging approach presented here, following Efron ( J. Amer. Statist. Assoc. 109 (2014) 991–1007). We investigate relative strengths and weaknesses of each method. The “Rubin’s Rules” multiple imputation estimator can have severe undercoverage, and is not recommended. The imputation-selection estimator with bootstrap percentile confidence intervals works well. The bootstrap-model-averaged estimator, with the “Efron’s Rules” estimated variance, may be preferred if the true effect sizes are moderate. We apply these results to the colorectal neoplasia risk-prediction problem which motivated the present work.

Cristiano Villa, Jeong Eun Lee.

Source: Bayesian Analysis, Volume 15, Number 2, 533--558.

Abstract:
In this work we propose a novel model prior for variable selection in linear regression. The idea is to determine the prior mass by considering the worth of each of the regression models, given the number of possible covariates under consideration. The worth of a model consists of the information loss and the loss due to model complexity. While the information loss is determined objectively, the loss expression due to model complexity is flexible and, the penalty on model size can be even customized to include some prior knowledge. Some versions of the loss-based prior are proposed and compared empirically. Through simulation studies and real data analyses, we compare the proposed prior to the Scott and Berger prior, for noninformative scenarios, and with the Beta-Binomial prior, for informative scenarios.

Qingpo Cai, Jian Kang, Tianwei Yu.

Source: Bayesian Analysis, Volume 15, Number 1, 79--102.

Abstract:
Selecting informative nodes over large-scale networks becomes increasingly important in many research areas. Most existing methods focus on the local network structure and incur heavy computational costs for the large-scale problem. In this work, we propose a novel prior model for Bayesian network marker selection in the generalized linear model (GLM) framework: the Thresholded Graph Laplacian Gaussian (TGLG) prior, which adopts the graph Laplacian matrix to characterize the conditional dependence between neighboring markers accounting for the global network structure. Under mild conditions, we show the proposed model enjoys the posterior consistency with a diverging number of edges and nodes in the network. We also develop a Metropolis-adjusted Langevin algorithm (MALA) for efficient posterior computation, which is scalable to large-scale networks. We illustrate the superiorities of the proposed method compared with existing alternatives via extensive simulation studies and an analysis of the breast cancer gene expression dataset in the Cancer Genome Atlas (TCGA).

Gemma E. Moran, Veronika Ročková, Edward I. George.

Source: Bayesian Analysis, Volume 14, Number 4, 1091--1119.

Abstract:
Consider the problem of high dimensional variable selection for the Gaussian linear model when the unknown error variance is also of interest. In this paper, we show that the use of conjugate shrinkage priors for Bayesian variable selection can have detrimental consequences for such variance estimation. Such priors are often motivated by the invariance argument of Jeffreys (1961). Revisiting this work, however, we highlight a caveat that Jeffreys himself noticed; namely that biased estimators can result from inducing dependence between parameters a priori . In a similar way, we show that conjugate priors for linear regression, which induce prior dependence, can lead to such underestimation in the Bayesian high-dimensional regression setting. Following Jeffreys, we recommend as a remedy to treat regression coefficients and the error variance as independent a priori . Using such an independence prior framework, we extend the Spike-and-Slab Lasso of Ročková and George (2018) to the unknown variance case. This extended procedure outperforms both the fixed variance approach and alternative penalized likelihood methods on simulated data. On the protein activity dataset of Clyde and Parmigiani (1998), the Spike-and-Slab Lasso with unknown variance achieves lower cross-validation error than alternative penalized likelihood methods, demonstrating the gains in predictive accuracy afforded by simultaneous error variance estimation. The unknown variance implementation of the Spike-and-Slab Lasso is provided in the publicly available R package SSLASSO (Ročková and Moran, 2017).

Mengyang Gu.

Source: Bayesian Analysis, Volume 14, Number 3, 877--905.

Abstract:
Gaussian stochastic process (GaSP) has been widely used in two fundamental problems in uncertainty quantification, namely the emulation and calibration of mathematical models. Some objective priors, such as the reference prior, are studied in the context of emulating (approximating) computationally expensive mathematical models. In this work, we introduce a new class of priors, called the jointly robust prior, for both the emulation and calibration. This prior is designed to maintain various advantages from the reference prior. In emulation, the jointly robust prior has an appropriate tail decay rate as the reference prior, and is computationally simpler than the reference prior in parameter estimation. Moreover, the marginal posterior mode estimation with the jointly robust prior can separate the influential and inert inputs in mathematical models, while the reference prior does not have this property. We establish the posterior propriety for a large class of priors in calibration, including the reference prior and jointly robust prior in general scenarios, but the jointly robust prior is preferred because the calibrated mathematical model typically predicts the reality well. The jointly robust prior is used as the default prior in two new R packages, called “RobustGaSP” and “RobustCalibration”, available on CRAN for emulation and calibration, respectively.

Quan Zhou, Yongtao Guan.

Source: Bayesian Analysis, Volume 14, Number 2, 573--594.

Abstract:
Bayesian variable selection regression (BVSR) is able to jointly analyze genome-wide genetic datasets, but the slow computation via Markov chain Monte Carlo (MCMC) hampered its wide-spread usage. Here we present a novel iterative method to solve a special class of linear systems, which can increase the speed of the BVSR model-fitting tenfold. The iterative method hinges on the complex factorization of the sum of two matrices and the solution path resides in the complex domain (instead of the real domain). Compared to the Gauss-Seidel method, the complex factorization converges almost instantaneously and its error is several magnitude smaller than that of the Gauss-Seidel method. More importantly, the error is always within the pre-specified precision while the Gauss-Seidel method is not. For large problems with thousands of covariates, the complex factorization is 10–100 times faster than either the Gauss-Seidel method or the direct method via the Cholesky decomposition. In BVSR, one needs to repetitively solve large penalized regression systems whose design matrices only change slightly between adjacent MCMC steps. This slight change in design matrix enables the adaptation of the iterative complex factorization method. The computational innovation will facilitate the wide-spread use of BVSR in reanalyzing genome-wide association datasets.

Alberto Cassese, Weixuan Zhu, Michele Guindani, Marina Vannucci.

Source: Bayesian Analysis, Volume 14, Number 2, 553--572.

Abstract:
In many applications, investigators monitor processes that vary in space and time, with the goal of identifying temporally persistent and spatially localized departures from a baseline or “normal” behavior. In this manuscript, we consider the monitoring of pneumonia and influenza (P&I) mortality, to detect influenza outbreaks in the continental United States, and propose a Bayesian nonparametric model selection approach to take into account the spatio-temporal dependence of outbreaks. More specifically, we introduce a zero-inflated conditionally identically distributed species sampling prior which allows borrowing information across time and to assign data to clusters associated to either a null or an alternate process. Spatial dependences are accounted for by means of a Markov random field prior, which allows to inform the selection based on inferences conducted at nearby locations. We show how the proposed modeling framework performs in an application to the P&I mortality data and in a simulation study, and compare with common threshold methods for detecting outbreaks over time, with more recent Markov switching based models, and with spike-and-slab Bayesian nonparametric priors that do not take into account spatio-temporal dependence.

Suprateek Kundu, Bani K. Mallick, Veera Baladandayuthapani.

Source: Bayesian Analysis, Volume 14, Number 2, 449--476.

Abstract:
There has been an intense development in the Bayesian graphical model literature over the past decade; however, most of the existing methods are restricted to moderate dimensions. We propose a novel graphical model selection approach for large dimensional settings where the dimension increases with the sample size, by decoupling model fitting and covariance selection. First, a full model based on a complete graph is fit under a novel class of mixtures of inverse–Wishart priors, which induce shrinkage on the precision matrix under an equivalence with Cholesky-based regularization, while enabling conjugate updates. Subsequently, a post-fitting model selection step uses penalized joint credible regions to perform model selection. This allows our methods to be computationally feasible for large dimensional settings using a combination of straightforward Gibbs samplers and efficient post-fitting inferences. Theoretical guarantees in terms of selection consistency are also established. Simulations show that the proposed approach compares favorably with competing methods, both in terms of accuracy metrics and computation times. We apply this approach to a cancer genomics data example.

A digital-savvy historian discusses his popular @HistOpinion Twitter account

Here's what you need to know to preserve your copy of history

Successful modification of the bacterial artificial chromosome (BAC) after two-step BAC engineering is confirmed in two separate polymerase chain reactions (PCRs). The first reaction (5' co-integrate PCR) uses a forward 5' co-integrate primer (a sequence located upstream of the 5' end of the A-box) and a reverse 3' primer on the vector (175PA+50AT) or within the reporter sequence or mutated region as appropriate. The second reaction (3' co-integrate PCR) uses a forward 5' primer on the recA gene (RecA1300S) and a reverse 3' co-integrate primer (a sequence located downstream from the 3' end of the B-box). Those colonies shown to be positive in PCR analysis are further tested for sensitivity to UV light. After the resolution, colonies that have lost the excised recombination vector including sacB and recA genes become UV light sensitive.

Everyone knows SOLIDWORKS is very flexible and user friendly to execute the commands to complete any 3D design easily. When it comes to handling Complex assemblies (Increased in number of components) many of us will search for special tools to

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The post SOLIDWORKS Quick tips – Advanced Component Selection appeared first on SOLIDWORKS Tech Blog.

There are 3 main tools that can project our 2D sketch onto a face: Project curve, Split line and Wrap. How should we choose and what is the difference between them? Here are some tips for you. Project curve –

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The post Best selection of sketch projection tools in SOLIDWORKS appeared first on SOLIDWORKS Tech Blog.

Bold steps can be taken by the EU to ease sanctions while not rewarding recalcitrant behaviour by Zanu-PF leadership

The pervasive fear of violence and intimidation in Zimbabwe’s 2013 elections contradicts political leaders’ rhetorical commitments to peace, and raises concerns that the country may not be ready to go to the polls.

A return to protracted political crisis, and possibly extensive violence, is likely as Zimbabwe holds elections on 31 July. conditions for a free and fair vote do not exist.

Hailed as transitional by local observers, the latest polls were expected to usher in a new type of leadership in FRELIMO, with Filipe Nyussi being the first non-liberation northern leader in a southern dominated elite; they would also see opposition parties RENAMO and MDM alter their strategies and become more politically relevant; and would possibly be the last polls before the country became a mass resource-producing economy. However, the Presidential and parliamentary elections of 15 October have made the political setting, the prospects for improved governance and wealth redistribution more opaque, and the implementation of the new peace agreement harder.

CNA Staff, May 5, 2020 / 10:00 am (CNA).- Poland’s bishops have intervened in a debate about whether presidential elections scheduled for May 10 should go ahead despite a nationwide lockdown.

A statement from the permanent council of the Polish bishops’ conference April 27 urged politicians to work together to ensure that the election would be regarded as legitimate by all sides. 

It said: “We appeal to the consciences of those responsible for the common good of our homeland, both those in power and the opposition, to work out a common position on the presidential elections in this extraordinary situation.” 

Poland’s ruling coalition, led by the Law and Justice (PiS) party, has rejected calls to postpone the election, due to take place this Sunday. 

The state began introducing lockdown measures March 10, which it is now starting to lift. Poland, which has a population of almost 38 million, had 14,242 documented coronavirus cases and 700 deaths as of May 5, according to Johns Hopkins University Coronavirus Resource Center.

The Polish Senate began debating legislation May 5 that would allow the election to be held by postal vote, rather than at polling stations, due to the pandemic. 

The Sejm, the lower chamber of the Polish parliament, will have the final say on the legislation. 

The bishops called on lawmakers to resolve the issue while upholding the principles of Poland’s constitution. They emphasized that they were not seeking to engage in “purely political disputes over the form or timing of election, let alone to advocate this or that solution.”

The bishops’ permanent council said: “We encourage dialogue between the parties to seek solutions that would not raise legal doubts and suspicion, not only of a violation of the current constitutional order but also of the principles of free and fair elections adopted in a democratic society.”

“We ask that, guided by the best will, they would seek in their actions the common good, which today is expressed both by the life, health and social existence of Poles, as well as broad social trust in the electoral procedures of a democratic state jointly developed over the years.”

The bishops continued: “In this difficult situation that we are experiencing, we should take care to cultivate a mature democracy, protect the nation of laws, building -- despite differences -- a culture of solidarity, also in the political sphere.”

If parliament approves the postal vote, the government could delay the vote to either May 17 or May 23 to allow more preparation time, according to Reuters. 

Opinion polls suggest the incumbent President Andrzej Duda, a PiS ally, would be re-elected by a significant margin if the vote were held soon. 

Bishops’ conference president Archbishop Stanisław Gądecki entrusted Poland to the Most Sacred Heart of Jesus and to Our Lady, Queen of Poland, at Jasna Góra Monastery in Częstochowa May 3.

The recent Chicago Teachers Union strike drew attention from Democratic presidential candidates in Illinois, a state won by Democrats in the last White House contest. For 2020, it's possible we could see a twist on that story: big-city teacher strikes in states with less predictable outcomes.

Both the AFT and the NEA vowed to engage their members more deeply this year in deciding who to back for the White House. How well have they done?

The highly polarizing 2016 Presidential campaign blitzed the swing state of Virginia. And in the year that followed, a new study in the journal Educational Researcher suggests school bullying problems likewise split along political lines.

The recent Chicago Teachers Union strike drew attention from Democratic presidential candidates in Illinois, a state won by Democrats in the last White House contest. For 2020, it's possible we could see a twist on that story: big-city teacher strikes in states with less predictable outcomes.

Both the AFT and the NEA vowed to engage their members more deeply this year in deciding who to back for the White House. How well have they done?

Ideal empirical antibiotic choices are based on local susceptibility data. These choices are important for ensuring positive patient outcomes, but pediatric-specific data may not be available.

Antibiotic susceptibilities differ by age group within a tertiary-care hospital. Knowing these differences, pediatricians chose empirical antibiotic therapy more likely to be successful. Children with infectious diseases would benefit from reporting of pediatric-specific susceptibility results. (Read the full article)

A previous study suggested that physicians in 1 practice network were less likely to diagnose otitis media (OM) and to prescribe broad-spectrum antibiotics for OM for black versus nonblack children.

Nationally, black children with OM are more likely to receive guideline-recommended, narrow-spectrum antibiotics than nonblack children. These findings may reflect inappropriate treatment of OM with the use of broad-spectrum antibiotics in a majority of US children. (Read the full article)

Education Week reporters Alyson Klein and Sean Cavanagh discuss the races to watch.